Diffraction measurement and analysis of slanted holographic polymer dispersed liquid crystal

Author name used in this publication: Xiao Hong SunAuthor name used in this publication: Xiao Ming TaoAuthor name used in this publication: Ting Jin YeAuthor name used in this publication: Xiao Yin Cheng2005-2006 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Topological correlations in soap froths

Correlation in two-dimensional soap froth is analysed with an effective potential for the first time. Cells with equal number of sides repel (with linear correlation) while cells with different number of sides attract (with NON-bilinear) for nearest neighbours, which cannot be explained by the maximum entropy argument. Also, the analysis indicates that froth is correlated up to the third shell neighbours at least, contradicting the conventional ideas that froth is not strongly correlated.Comment: 10 Pages LaTeX, 6 Postscript figure

Massively parallel determination and modeling of endonuclease substrate specificity

We describe the identification and characterization of novel homing endonucleases using genome database mining to identify putative target sites, followed by high throughput activity screening in a bacterial selection system. We characterized the substrate specificity and kinetics of these endonucleases by monitoring DNA cleavage events with deep sequencing. The endonuclease specificities revealed by these experiments can be partially recapitulated using 3D structure-based computational models. Analysis of these models together with genome sequence data provide insights into how alternative endonuclease specificities were generated during natural evolution

Comparing the reliability of networks by spectral analysis

We provide a method for the ranking of the reliability of two networks with the same connectance. Our method is based on the Cheeger constant linking the topological property of a network with its spectrum. We first analyze a set of twisted rings with the same connectance and degree distribution, and obtain the ranking of their reliability using their eigenvalue gaps. The results are generalized to general networks using the method of rewiring. The success of our ranking method is verified numerically for the IEEE57, the Erd\H{o}s-R\'enyi, and the Small-World networks.Comment: 7 pages, 3 figure

Ground-layer wavefront reconstruction from multiple natural guide stars

Observational tests of ground layer wavefront recovery have been made in open loop using a constellation of four natural guide stars at the 1.55 m Kuiper telescope in Arizona. Such tests explore the effectiveness of wide-field seeing improvement by correction of low-lying atmospheric turbulence with ground-layer adaptive optics (GLAO). The wavefronts from the four stars were measured simultaneously on a Shack-Hartmann wavefront sensor (WFS). The WFS placed a 5 x 5 array of square subapertures across the pupil of the telescope, allowing for wavefront reconstruction up to the fifth radial Zernike order. We find that the wavefront aberration in each star can be roughly halved by subtracting the average of the wavefronts from the other three stars. Wavefront correction on this basis leads to a reduction in width of the seeing-limited stellar image by up to a factor of 3, with image sharpening effective from the visible to near infrared wavelengths over a field of at least 2 arc minutes. We conclude that GLAO correction will be a valuable tool that can increase resolution and spectrographic throughput across a broad range of seeing-limited observations.Comment: 25 pages, 8 figures, to be published in Astrophys.

Defining NELF-E RNA binding in HIV-1 and promoter-proximal pause regions

The four-subunit Negative Elongation Factor (NELF) is a major regulator of RNA Polymerase II (Pol II) pausing. The subunit NELF-E contains a conserved RNA Recognition Motif (RRM) and is proposed to facilitate Poll II pausing through its association with nascent transcribed RNA. However, conflicting ideas have emerged for the function of its RNA binding activity. Here, we use in vitro selection strategies and quantitative biochemistry to identify and characterize the consensus NELF-E binding element (NBE) that is required for sequence specific RNA recognition (NBE: CUGAGGA(U) for Drosophila). An NBE-like element is present within the loop region of the transactivation-response element (TAR) of HIV-1 RNA, a known regulatory target of human NELF-E. The NBE is required for high affinity binding, as opposed to the lower stem of TAR, as previously claimed. We also identify a non-conserved region within the RRM that contributes to the RNA recognition of Drosophila NELF-E. To understand the broader functional relevance of NBEs, we analyzed promoter-proximal regions genome-wide in Drosophila and show that the NBE is enriched +20 to +30 nucleotides downstream of the transcription start site. Consistent with the role of NELF in pausing, we observe a significant increase in NBEs among paused genes compared to non-paused genes. In addition to these observations, SELEX with nuclear run-on RNA enrich for NBE-like sequences. Together, these results describe the RNA binding behavior of NELF-E and supports a biological role for NELF-E in promoter-proximal pausing of both HIV-1 and cellular genes

Prognostic Value of Immune Environment Analysis in Small Bowel Adenocarcinomas with Verified Mutational Landscape and Predisposing Conditions

Background: Small bowel adenocarcinoma (SBA) is a rare yet insidious cancer with poor survival. The abundance of tumour-infiltrating lymphocytes is associated with improved survival, but the role of the programmed death-1/programmed death ligand-1 (PD-1/PD-L1) pathway in tumour escape is controversial. We evaluated immune cell infiltration, PD1/PD-L1 expression and their prognostic value in a series of SBAs with previously verified predisposing conditions and exome-wide somatic mutation characterization. Methods: Formalin-fixed paraffin-embedded tissue sections stained for CD3, CD8, PD-L1 and PD-1 were analysed from 94 SBAs. An immune cell score (ICS) was formed from the amount of the CD3 and CD8 positive lymphocytes from the tumour centre and invasive margin. The PD-L1 and PD-1 positive immune cells (ICs) and ICS were combined into a variable called Immunoprofile. Results: High ICS, PD-L1IC and PD-1, individually and combined as Immunoprofile, were prognostic for better patient outcome. Sixty-five (69%) SBAs expressed ≥1% positive PD-L1IC. A high tumour mutation burden was common (19%) and associated with immune markers. Immunoprofile, adjusted for TNM stage, mismatch repair status, tumour location, sex and age were independent prognostic markers for disease-specific and overall survival. Conclusions: Analysing tumoral immune contexture provides prognostic information in SBA. Combining ICS, PD-1 and PD-L1IC as Immunoprofile enhanced the prognostic performance

Targeting mitochondria by ss-31 ameliorates the whole body energy status in cancer-and chemotherapy-induced cachexia

Objective: Cachexia is a complex metabolic syndrome frequently occurring in cancer patients and exacerbated by chemotherapy. In skeletal muscle of cancer hosts, reduced oxidative ca-pacity and low intracellular ATP resulting from abnormal mitochondrial function were described. Methods: The present study aimed at evaluating the ability of the mitochondria-targeted compound SS-31 to counteract muscle wasting and altered metabolism in C26-bearing (C26) mice either receiv-ing chemotherapy (OXFU: oxaliplatin plus 5-fluorouracil) or not. Results: Mitochondrial dysfunction in C26-bearing (C26) mice associated with alterations of cardiolipin fatty acid chains. Selectively targeting cardiolipin with SS-31 partially counteracted body wasting and prevented the reduction of glycolytic myofiber area. SS-31 prompted muscle mitochondrial succinate dehydrogenase (SDH) activity and rescued intracellular ATP levels, although it was unable to counteract mitochondrial protein loss. Progressively increased dosing of SS-31 to C26 OXFU mice showed transient (21 days) beneficial effects on body and muscle weight loss before the onset of a refractory end-stage condi-tion (28 days). At day 21, SS-31 prevented mitochondrial loss and abnormal autophagy/mitophagy. Skeletal muscle, liver and plasma metabolomes were analyzed, showing marked energy and protein metabolism alterations in tumor hosts. SS-31 partially modulated skeletal muscle and liver metab-olome, likely reflecting an improved systemic energy homeostasis. Conclusions: The results suggest that targeting mitochondrial function may be as important as targeting protein anabolism/catabo-lism for the prevention of cancer cachexia. With this in mind, prospective multi-modal therapies including SS-31 are warranted